Extending physical activity behavior change studies to include outcomes related to health and well-being assess whether the physical activity increases are adequate for improved health. Moreover, few studies have examined cytokine changes in cancer survivors after participation in a physical activity behavior change intervention with a mechanistic focus on cytokines which may influence the muscle strength, fatigue, and sleep response to the intervention. Therefore, a randomized controlled trial with the following study aims is proposed: Study aim 1: The intervention group will be compared with the control group to examine the change in physical activity, muscle strength, fatigue, and sleep dysfunction before and after participation in a physical activity behavior change intervention. We hypothesize that as compared with the control group, the intervention group will demonstrate an increase in muscle strength and a decrease in fatigue and sleep dysfunction. Based on pilot data, we further hypothesize that the change in fatigue and sleep dysfunction will vary based on dimension assessed (e.g., improvements with the intervention may be greatest for the dimensions of "average fatigue over the past week", self-reported sleep efficiency, and accelerometer measured sleep latency). Study aim 2: To investigate mechanisms that may underlie the effects of the physical activity behavior change intervention on muscle strength, fatigue, and sleep, we will compare the intervention group with the control group in terms of changes in cytokine markers of inflammation and evaluate whether such changes are consistent with and may mediate changes in muscle strength, fatigue, and sleep dysfunction. The cytokines we will measure were selected based on their associations with muscle strength response to exercise training, fatigue, and sleep dysfunction and our ability to detect these cytokines during pilot testing. Tumor necrosis factor (TNF)-1, interleukin (IL)-6, IL-8, and IL-10 will be measured in serum. Based on preliminary data and literature review, we hypothesize that the intervention will increase IL-6 and reduce IL-8, TNF-1, and IL-10. Although IL-10 is an anti-inflammatory cytokine, we speculate that it will be reduced due to the feedback loop between IL-10 and pro-inflammatory cytokines such as TNF. We also hypothesize that changes in these cytokines will mediate, at least in part, the intervention effects on the measured health outcomes. Seventy-four female, breast cancer survivors will be randomized. Measures include physical activity (accelerometer and self-report), muscle strength, fatigue, sleep (accelerometer and self-report), and serum cytokine levels (Luminex(r) multiplex technology). Potential covariates will be assessed. Mixed model ANOVA and mediation analyses with the Freedman-Schatzkin difference-in-coefficients test will be performed. This R21 proposal will suggest mechanistic theories underlying the benefits of biobehavioral interventions and provide the required effect size information for designing the adequately powered R01 trials required to test these theoretical mechanisms. PUBLIC HEALTH RELEVANCE: It is important to confirm health benefits experienced by breast cancer survivors after participation in a physical activity behavior change intervention. Such benefits may include improved strength, less tiredness, and better sleep. Also, few scientists have studied how inflammation in breast cancer survivors may influence the effect of physical activity on these benefits. Such information has the potential to lead to a better understanding of why physical activity is beneficial and enhance ways to help improve physical functioning and reduce bothersome symptoms (e.g., fatigue, poor sleep) in breast cancer survivors.